The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.
Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
176
20 mg/kg/day over one year in patients with MDS
Number of Participants Reporting Adverse Events
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
Time frame: up to 53 Weeks
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).
Time frame: From Baseline to Weeks 13, 25, 37 and 53
Change in Labile Plasma Iron (LPI)
LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe
Time frame: From Baseline to Weeks 13, 25, 37 and 49
Directly Chelatable Iron (DCI)
The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.
Time frame: From Baseline to Weeks 13, 25, 37 and 49
Total Iron Levels
Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.
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Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Serum Transferrin Levels
Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.
Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Transferrin Saturation
Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.
Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Transfusion Requirements
Number of participants receiving transfusions, the summarized during the study.
Time frame: up to 1 year
Frequency of Hematologic Improvement During the Study
Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, \<11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,\<100x10\^9/L): If starting with \>20x10\^9/L platelets: absolute increase 30x10\^9/L, Increase from baseline \<20 x10\^9/L to \>20x10\^9/L and by =/\> 100%; Neutrophil response (pretreatment, \<1.0x10\^9/L): =/\> 100% increase \& absolute increase \>0.5x10\^9/L; Progression or relapse after HI: At least 1 of the following: =/\>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.
Time frame: up to 1 year
Trough Plasma Deferasirox Concentration
The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.
Time frame: At Week 13, 25, 37 and 49
Treatment Compliance to Deferasirox
Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.
Time frame: up to 1 year
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.
Time frame: up to Week 13 (Month 3)